Landscape of transcription in human cells.

Centre for Genomic Regulation and UPF, Doctor Aiguader 88, Barcelona 08003, Catalonia, Spain.
Nature (Impact Factor: 42.35). 09/2012; 489(7414):101-8. DOI: 10.1038/nature11233
Source: PubMed

ABSTRACT Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To discuss the effectiveness and safety of swift needling with fire needle plus medication in treating herpes zoster and the change of substance P. Methods Seventy-nine patients with herpes zoster were selected and randomized into a fire-acupuncture group (41 cases) and a Western-medication group (38 cases). The fire-acupuncture group was intervened by swift needling with fire needle, and simultaneously prescribed with Valaciclovir Hydrochloride tablets and Vitamin B1; the Western-medication group was by the same oral medicines alone. The therapeutic efficacies were evaluated afterwards. Results The total effective rate was 95.1% in the fire-acupuncture group versus 89.5% in the Western-medication group, and the difference was statistically significant (PPP Conclusion Swift needling with fire needle plus medication has better therapeutic efficacy than medication alone in treating herpes zoster.
    Journal of Acupuncture and Tuina Science 12/2013; 11(6):380-383.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Transposable elements (TEs) have significantly influenced the evolution of transcriptional regulatory networks in the human genome. Post-transcriptional regulation of human genes by TE-derived sequences has been observed in specific contexts, but has yet to be systematically and comprehensively investigated. Here, we study a collection of 75 CLIP-Seq experiments mapping the RNA binding sites for a diverse set of 51 human proteins to explore the role of TEs in post-transcriptional regulation of human mRNAs and lncRNAs via RNA-protein interactions. We detect widespread interactions between RNA binding proteins (RBPs) and many families of TE-derived sequence in the CLIP-Seq data. Further, alignment coverage peaks on specific positions of the TE consensus sequences, illuminating a diversity of TE-specific RBP binding motifs. Evidence of binding and conservation of these motifs in the nonrepetitive transcriptome suggests that TEs have generally appropriated existing sequence preferences of the RBPs. Depletion assays for numerous RBPs show that TE-derived binding sites affect transcript abundance and splicing similarly to nonrepetitive sites. However, in a few cases the effect of RBP binding depends on the specific TE family bound; for example, the ubiquitously expressed RBP HuR confers transcript stability unless bound to an Alu element. Our meta-analysis suggests a widespread role for TEs in shaping RNA-protein regulatory networks in the human genome.
    Genome Biology 12/2014; 15(12):537. · 10.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have been well characterized. In these cases, lncRNAs have been shown to be key regulators of several cellular processes. Therefore, there is a great need to understand the function of more lncRNAs and their regulation in response to stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response. IFN binding to its receptor activates transcription of several IFN-stimulated genes (ISGs) that function as potent antivirals. In addition, several ISGs are positive or negative regulators of the IFN pathway. This is essential to ensure a strong antiviral response and a later return of the cell to homeostasis. As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. The results show that IFN-treatment regulates the expression of several unknown non-coding transcripts. We have validated two lncRNAs upregulated after treatment with different doses of type I IFNα2 in different cells or with type III IFNλ. These lncRNAs were also induced by influenza and vesicular stomatitis virus mutants unable to block the IFN response, but not by several wild-type lytic viruses tested. These lncRNA genes were named lncISG15 and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively. Interestingly, inhibition experiments showed that lncBST2 is a positive regulator of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated positive regulator. Our results may have therapeutic implications as lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in cells infected with hepatitis C virus and in the liver of infected patients. These results allow us to hypothesize that several lncRNAs could be activated by IFN to control the potency of the antiviral IFN response.
    Frontiers in Immunology 01/2014; 5:655.

Full-text (2 Sources)

Available from
May 21, 2014